The experience of negative emotions is associated with an increased risk of incident atherosclerosis-related cardiovascular disease (CVD) events, independent of traditional risk factors. The strongest data supporting this relation is with provoked anger. There is also some evidence that becoming acutely depressed or anxious are also triggers of incident CVD. The underlying putative mechanisms are poorly understood. Vascular endothelial cells (ECs) play an essential role in maintaining vascular tone and the integrity of blood vessels. Evidence suggests that dysfunction of the endothelium is an early pathogenic process underlying atherosclerosis development and CVD event onset. The aims of this study are to primarily examine the acute effects of provoked anger and secondarily depressed mood and anxiety on EC health. Examination of these critical pathways will help determine whether endothelial dysfunction is a biological mechanism linking the experience of core negative emotions and incident CVD risk. In this application, a state-of-the-art, laboratory-based, randomized controlled experiment is proposed that will test whether provoked anger, depressed mood and anxiety will induce endothelial dysfunction in humans. We hypothesize that compared to an emotionally neutral condition; an anger recall task will impair endothelium-dependent vasodilatation, injure ECs, and reduce EC reparative capacity. We will also examine whether a depressed mood and anxiety induction task will similarly induce endothelial dysfunction, as well as whether levels of provoked self-reported anger, depressed mood, and anxiety are associated with the degree of endothelial dysfunction. Finally, given that endogenous nitric oxide (NO) inhibition plays a central role in exacerbating endothelial dysfunction, we will explore whether NO inhibition partially mediates the acute adverse effects of provoked anger, depressed mood, and anxiety on endothelial function. In the United States, atherosclerosis-related CVD events remain the leading cause of morbidity and mortality. Further, anger, depressed mood, and anxiety are negative emotions commonly experienced by adults in the general population on a day-to-day basis. Therefore, evaluation of these hypotheses is timely and highly significant, as it will help identify a putative biological pathway linking the experience of core negative emotions to CVD incidence, for a large number of individuals who are at increased risk for CVD events.